U.S. patent number 6,808,506 [Application Number 10/357,502] was granted by the patent office on 2004-10-26 for device and method for delivering or withdrawing a substance through the skin.
This patent grant is currently assigned to Becton, Dickinson and Company, Becton, Dickinson and Company. Invention is credited to James K. Fentress, Julia Griggs, M. Ishaq Haider, Alexander G. Lastovich, Frank E. Martin, Ronald J. Pettis, Diane Sutter.
United States Patent |
6,808,506 |
Lastovich , et al. |
October 26, 2004 |
Device and method for delivering or withdrawing a substance through
the skin
Abstract
An apparatus for delivering or withdrawing a fluid through at
least one layer of the skin is provided. A device includes a body
having a top face, a bottom face, a side edge and at least one
channel. The bottom face includes a first surface area and a second
surface area adjacent to and recessed at a first distance from the
first surface area. The bottom face further includes at least one
raised protrusion disposed on the second surface area. The
protrusion has a height from the first surface greater than the
first distance. At least one dermal-access member is provided in
the protrusion and is in fluid communication with the channel to
deliver or withdraw the fluid. The dermal-access member extends at
least 1 mm from the protrusion. A mechanism drives the device
against the skin at a calculated speed of about 6 m/s to about 18
m/s.
Inventors: |
Lastovich; Alexander G.
(Raleigh, NC), Fentress; James K. (Morrisville, NC),
Griggs; Julia (Morrisville, NC), Pettis; Ronald J.
(Cary, NC), Sutter; Diane (Cary, NC), Martin; Frank
E. (Durham, NC), Haider; M. Ishaq (Morrisville, NC) |
Assignee: |
Becton, Dickinson and Company
(Franklin Lakes, NJ)
|
Family
ID: |
27739508 |
Appl.
No.: |
10/357,502 |
Filed: |
February 4, 2003 |
Current U.S.
Class: |
604/47 |
Current CPC
Class: |
A61M
5/14244 (20130101); A61M 37/0015 (20130101); A61M
5/425 (20130101); A61M 5/3007 (20130101); A61M
5/46 (20130101) |
Current International
Class: |
A61B
17/20 (20060101); A61M 37/00 (20060101); A61M
31/00 (20060101); A61M 35/00 (20060101); A61B
017/20 () |
Field of
Search: |
;604/46,47,506 ;606/186
;600/583 ;424/449 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
Primary Examiner: Kennedy; Sharon
Attorney, Agent or Firm: Becton, Dickinson and Company
Anderson, Esq.; Chad C.
Parent Case Text
CROSS-REFERENCE TO RELATED APPLICATIONS
The present application is related to and claims priority to the
following U.S. Provisional Patent Applications, identified by
Application No. and filing date: 60/353,194, filed Feb. 4, 2002;
60/397,038, filed Jul. 22, 2002; 60/407,284, filed Sep. 3, 2002;
60/420,233, filed Oct. 23, 2002; 60/377,649 filed May 6, 2002; and
60/389,881, filed Jun. 20, 2002. The contents of each of the
foregoing documents are incorporated herein by reference in their
entirety.
Claims
What is claimed is:
1. An apparatus for delivering or withdrawing a fluid through at
least one layer of the skin of a subject, the apparatus comprising:
a device comprising a body having a top face, a bottom face spaced
from the top face, and a side edge, the body defining at least one
channel, wherein the bottom face includes a first surface area and
a second surface area adjacent to and recessed at a first distance
from the first surface area, the bottom face further including at
least one raised protrusion disposed on the second surface area,
the at least one raised protrusion having a height from the first
surface, and the height being greater than the first distance; at
least one dermal-access member provided in the at least one raised
protrusion and being in fluid communication with the channel to
deliver or withdraw the fluid, the at least one dermal-access
member extending at least 1 mm from the at least one protrusion;
and means for driving the device against the skin at a calculated
speed of about 6 m/s to about 18 m/s.
2. The apparatus of claim 1, wherein the at least one raised
protrusion is a conical protrusion with a flattened upper surface
having a diameter of less than 2 mm.
3. The apparatus of claim 2, wherein the flattened upper surface
has a diameter of about 1 mm.
4. The apparatus of claim 1, wherein the at least one dermal-access
member extends about 3 mm from the at least one protrusion.
5. The apparatus of claim 1, wherein the driving means drives the
device against the skin at a calculated speed of about 12 m/s.
6. The apparatus of claim 1, wherein the second distance is at
least about 0.5 mm greater than the first distance.
7. The apparatus of claim 1, wherein the second distance is at
least about 1 mm greater than the first distance.
8. The apparatus of claim 1, wherein said driving means includes a
coil spring.
9. The apparatus of claim 1, wherein the device includes a
plurality of protrusions and one dermal-access member is provided
in each protrusion, and wherein the dermal-access member of a
respective protrusion is of a different length from the
dermal-access member of another protrusion, the lengths of the
dermal-access members being of sufficient lengths to deliver or
withdraw the fluid from a subcutaneous layer of the skin and an
intradermal layer of the skin.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a device and a method for
delivering or withdrawing a substance through the skin of an
animal, including humans, and in particular to a method and device
for withdrawing or delivering a substance such as a drug, protein
or vaccine to a subject. The invention also relates to a device for
enhancing the penetration of one or more dermal-access members.
2. Related Art
The skin is made up of several layers with the upper composite
layer being the epithelial layer. The outermost layer of the skin
is the stratum corneum that has well known barrier properties to
prevent molecules and various substances from entering the body and
analytes from exiting the body. The stratum corneum is a complex
structure of compacted keratinized cell remnants having a thickness
of about 10-30 microns. The stratum corneum forms a waterproof
membrane to protect the body from invasion by various substances
and the outward migration of various compounds.
The natural impermeability of the stratum corneum prevents the
administration of most pharmaceutical agents and other substances
through the skin. Numerous methods and devices have been proposed
to enhance the permeability of the skin and to increase the
diffusion of various substances through the skin in order to be
utilized by the body. According to some methods and devices, the
delivery of substances through the skin is enhanced by either
increasing the permeability of the skin or increasing the force or
energy used to direct the substance through the skin.
Other methods of sampling and delivering various substances through
the skin include forming micropores or cuts through the stratum
corneum. Numerous substances can be effectively administered by
piercing the stratum corneum and delivering a substance in or below
the stratum corneum. In a similar manner, some substances can be
extracted from the body through cuts or pores formed in the stratum
corneum. The devices for piercing the stratum corneum generally
include a plurality of microneedles or blades having a length to
pierce the stratum corneum. Examples of these devices are disclosed
in U.S. Pat. No. 5,879,326 to Godshall et al.; U.S. Pat. No.
6,494,865 to Alchas; U.S. Pat. No. 5,997,501 to Gross et al.; U.S.
Pat. No. 4,886,499 to Cirelli et al.; U.S. Pat. No. 6,183,434 to
Eppstein; U.S. Pat. No. 5,250,023 to Lee et al.; International
publication WO 97/48440; U.S. Pat. No. 5,527,288 to Gross et al.;
and U.S. Pat. No. 3,595,231 to Pistor. Each of the,foregoing
documents is incorporated herein by reference in their
entirety.
Some of the above-noted devices include micron-sized needles or
blades and can be effective in delivering or sampling substances.
However, many of these needles and blades have a length of a few
microns to a few hundred microns and typically do not penetrate the
skin to a uniform depth. The natural elasticity and resilience of
the skin often result in the skin being deformed by the needles
rather than pierced. Therefore, when a microneedle array is pressed
against the skin, the outermost needles penetrate the skin while
the innermost needles do not penetrate the skin or only penetrate
to a depth less than the outermost needles.
Moreover, conventional devices have problems with overall height
and ease of use. As a result, the prior methods and devices for the
sampling and administering of substances have exhibited limited
success. Accordingly, a continuing need exists in the industry for
an improved device for the sampling and administering of various
substances to the body.
SUMMARY OF THE INVENTION
These and other objects are accomplished by a method and device
according to the present invention.
A device for delivering or withdrawing a substance, typically a
fluid, below the stratum corneum is provided. A body of the device
includes a top face, a bottom face spaced from the top face, and a
side edge. Typically, a channel is defined within the body. The
bottom face includes a first surface area and a second surface area
adjacent to and recessed from the first surface area. The bottom
face further includes at least one raised protrusion disposed on
the second surface area. At least one dermal-access member is
provided in each raised protrusion and is in fluid communication
with the channel to deliver or withdraw the substance.
Similarly, a method of delivering or withdrawing a substance
through at least one layer of the skin of a subject is provided.
The method includes the steps of: providing a device having a body
having a top face, a bottom face spaced from the top face, and a
side edge, the body defining a channel within the body, and at
least one dermal-access member coupled to and extending outwardly
from said bottom face and being in fluid communication with the
channel, wherein the bottom face includes a first surface area and
a second surface area adjacent to and recessed from the first
surface area, the bottom face further including at least one raised
protrusion disposed on the second surface area, at least one
dermal-access member installed in at least one raised protrusion;
positioning the dermal-access member on a target site of the skin
of the subject; applying a pressure against the device sufficient
for at least one dermal-access member to penetrate the skin and for
the first surface area to contact the skin; and delivering a
substance to or withdrawing a substance from the target side of the
subject.
In particular, a method and apparatus for delivering a substance,
such as a drug, protein or vaccine, into or below the stratum
corneum of the skin to a sufficient depth where the substance can
be absorbed and utilized by the body is provided.
The device and method according to an embodiment of the present
invention are suitable for use in administering various substances,
including pharmaceutical and bioactive agents, to a subject,
preferably a mammal, and particularly to a human patient. Such
substances have biological activity and can be delivered through
the body membranes and surfaces, and particularly the skin.
Examples include, but are not limited to antibiotics, antiviral
agents, analgesics, anesthetics, anorexics, antiarthritics,
antidepressants, antihistamines, anti-inflammatory agents,
antineoplastic agents, vaccines, including DNA vaccines, and the
like. Additional substances that can be delivered to a subject
include proteins, peptides and fragments thereof. The proteins and
peptides can be naturally occurring, synthesized or produced by
recombination.
The device and method may also be used for withdrawing a substance
or monitoring the level of a substance in the body. Examples of
substances that can be monitored or withdrawn include blood,
interstitial fluid or plasma. The withdrawn substances may then be
analyzed for various components or properties.
The dermal-access member according to the invention is any member
which penetrates the skin of a subject to the desired targeted
depth within a predetermined space without passing through it. In
most cases, the device will penetrate the skin to a depth of about
0.3-3 mm. Generally, the device is utilized for intradermal
administration, for example, with a configuration sufficient to
penetrate at a depth of about 1.0-1.7 mm. However, the device can
also be used to deliver a substance to a depth of about 0.3 mm or
less and at subcutaneous depths of 1.7 mm-3.0 mm depths or
greater.
The dermal-access members may comprise conventional injection
needles, catheters or microneedles of all known types, employed
singularly or in multiple member arrays. The terms "dermal-access
member" and "dermal-access members" as used herein are intended to
encompass all such needle-like structures. The dermal-access
members can include structures smaller than about 28 gauge,
typically about 29-50 gauge when such structures are cylindrical in
nature. Generally, the dermal access members will be about 30-36
gauge. Non-cylindrical structures encompassed by the term
dermal-access member would therefore be of comparable diameter and
include pyramidal, rectangular, octagonal, wedged, triangular,
hexagonal, cylindrical, tapered and other geometrical shapes and
arrangements. For example, the dermal-access members can be
microtubes, lancets and the like. Any suitable delivery mechanism
can be provided for delivering the substance to the penetrated
skin.
By varying the targeted depth of delivery of substances by the
dermal-access members, pharmacokinetic and pharmacodynamic (PK/PD)
behavior of the drug or substance can be tailored to the desired
clinical application most appropriate for a particular patient's
condition. The targeted depth of delivery of substances by the
dermal-access members may be controlled manually by the
practitioner, with or without the assistance of an indicator
mechanism to indicate when the desired depth is reached. Preferably
however, the device has structural mechanisms for controlling skin
penetration to the desired depth. This is most typically
accomplished by means of a widened area or hub associated with the
shaft of the dermal-access member that may take the form of a
backing structure or platform to which the dermal-access members
are attached. The length of dermal-access members are easily varied
during the fabrication process and are routinely produced at less
than 3 mm in length. The dermal-access members are typically sharp
and of a very small gauge, to further reduce pain and other
sensation when the dermal-access members are seated in the patient.
The invention may include a single-lumen dermal-access member or
multiple dermal-access members assembled or fabricated in linear
arrays or two- or three-dimensional arrays to increase the rate of
delivery or the amount of substance delivered in a given period of
time. Dermal-access members may be incorporated into a variety of
devices such as holders and housings that may also serve to limit
the depth of penetration. The dermal-access members of the
invention may also incorporate or be in fluid communication with
reservoirs to contain the substance prior to delivery or pumps or
other means for delivering the substance into the patient under
pressure. Alternatively, the dermal-access members may be linked
externally to such additional components.
The device may include a luer type or other connection port for
connection to a fluid delivery system such as a syringe, a pump, or
a pen. In such an embodiment, the device may use a length of tubing
for feeding a low dead volume body through an opening in the
body.
Any suitable mechanism for delivering a fluid to the dermal-access
members can be used. For example, a luer connection can be secured
directly to the device for delivering a fluid from tubing or
directly from a syringe secured to the luer connection.
Furthermore, the device or portions of the device can be
incorporated into an applicator that applies the device to a
patient in a consistent manner, for example, at a consistent
pressure, velocity and dose.
As an option, a removable shield can protect the device and
particularly, the dermal-access members until use.
In addition to being a useful device for penetrating skin at an
exact depth and for supplying an exact amount of fluid, the device
is useful in enabling the placement of multiple dermal-access
members simultaneously in a patient. This type of application is
useful in both device and drug testing applications.
When the device is used to deliver substances to the intradermal
space of a patient, the delivery of the substance typically results
in one or more blebs left in the skin. As used herein, bleb refers
to any site of deposition of a substance below the stratum corneum
of the skin, generally in the intradermal space. Typically, the
bleb extends laterally from the point of administration and
distends upward. The bleb diameter and height are functions of
instilled volume and rate of delivery and other factors. Secondary
physiology effects, such as irritation or histamine release, can
also alter bleb dimensions. Bleb duration can be a function of
uptake distribution and clearance of the instilled components, both
individually and in combination. Multiple blebs can be either
overlapping or non-overlapping. Non-overlapping blebs allow for
increased area of administration, but may contribute to imbalanced
flow to individual points of administration within a system.
Overlapping blebs may contribute to increase distension of tissue
space, and result in better equilibrium of infusion pressure, but
limits the benefits of increased fluid volume.
The device is constructed for penetrating selected layers of the
dermis of a subject to a desired depth. The desired depth of
penetration is usually determined by the substance being delivered
or withdrawn and the target site. In this manner, a substance can
be delivered, absorbed and utilized by the body substantially
without pain or discomfort to the subject.
The advantages and other salient features of the invention will
become apparent from the following detailed description which,
taken in conjunction with the annexed drawings, discloses preferred
embodiments of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
The following is a brief description of the drawings.
FIG. 1 is a perspective view of the device in accordance with an
embodiment of the invention for sampling or delivering a substance
through the skin of a subject.
FIG. 2 is an enlarged view of the bottom face of the device shown
in FIG. 1.
FIG. 3 is a side elevational view showing the device of FIG. 1
interfacing with the skin of a subject.
FIG. 4 is a view of the bleb pattern formed after application of
the device in FIG. 3.
FIG. 5 is a view of the bottom face of a further embodiment of the
device.
FIG. 6 is an exploded perspective view of an alternate embodiment
of the device.
FIG. 7 is a perspective view of the embodiment of the device shown
in FIG. 6.
FIG. 8 shows perspective views of the top face and the bottom face
of another embodiment of the device.
FIG. 9 is an enlarged perspective view of the bottom face of
another embodiment of the device.
FIG. 10 is a perspective view of the top and bottom faces of
another embodiment of the device.
FIG. 11 is a perspective view of the top and bottom faces of a
further embodiment of the device.
FIG. 12 is a perspective view of the top and bottom faces of an
additional embodiment of the device.
FIG. 13 is a perspective view of the device of FIG. 12 with
additional assembled components.
FIG. 14 is a perspective view of the top and bottom faces of a
further embodiment of the device.
FIG. 15 is a perspective view of the top and bottom faces of a
further embodiment of the device.
FIG. 16 is a perspective view of another embodiment of the
dermal-access member array of the device.
FIG. 17 is a table of results for an experiment indicating the
effectiveness of one aspect of the present invention.
FIGS. 18A-D are tables of results for an experiment indicating the
effectiveness of one aspect of the present invention.
FIG. 19 is a table of results for an experiment indicating the
effectiveness of one aspect of the present invention.
DETAILED DESCRIPTION OF AN EXEMPLARY EMBODIMENT OF THE PRESENT
INVENTION
A preferred embodiment of the invention is discussed in detail
below. While specific exemplary embodiments are discussed, it
should be understood that this is done for illustration purposes
only. A person skilled in the relevant art will recognize that
other components and configurations can be used without parting
from the spirit and scope of the invention.
Referring to the drawings, particularly FIGS. 1 and 2, a first,
exemplary embodiment of the invention is now described. As
described herein and shown in all of the figures, analogous or
identical features are indicated by the same reference number.
A device 10 according to the present invention has a body 12 and
dermal-access members 14. The device 10 optionally includes tubing
21 for delivering fluid to or removing fluid from the body 12 of
the device.
The body 12 optionally has a low profile to lie flat against the
skin of a subject. The low profile of the body 12 provides for ease
of attachment to the skin and less obstruction to the subject. The
low profile can be achieved by reducing the thickness of the body
12. In the embodiment shown, the body 12 has a substantially
circular disk shape, although in alternative embodiments, the body
12 can have a non-circular or other more angular shape or be
slightly arcuate. As an example, the diameter of the circular body
12 is preferably about 1-10 cm or less, although other sizes and
shapes can be used. Embodiments can be manufactured with diameters
of 5 mm or smaller.
The body 12, as shown in FIG. 2, has a circular outer side edge 16,
a top face 20 and a bottom face 18. The outer side edge 16
preferably has a rounded surface. The rounded surface helps control
the pressure distribution on the device 10 and subject during
application. Tapering and contouring help tension the skin at a
controlled rate to allow the dermal-access members 14 to penetrate
the skin with less force than would otherwise be required.
One or more fluid channels 22 are provided in the body 12. The
fluid channel 22 has an open inlet end 24. A coupling member 26 is
optionally provided for coupling a fluid delivery mechanism to the
body 12 at the open inlet end 24. Alternatively, no coupling member
is provided and the fluid delivery mechanism is secured directly to
the body 12. An axis of the fluid channel 22 optionally extends
substantially parallel to the plane of the body 12. In this manner,
the body 12 maintains a substantially flat, low profile
configuration. Of course, other arrangements of the coupling member
26 and the fluid channel 22 are possible.
In the embodiment shown in FIGS. 1 and 2, the bottom face 18 of the
body 12 has first 28 and second 30 surface areas. The first surface
area 28 is raised from the body 12 with respect to the second
surface area 30. Thus, the second surface area 30 defines a
recessed area on the bottom face 18 relative to the first surface
area 28.
Raised protrusions 32 are provided in the recessed second surface
area 30. As an exemplary embodiment, each protrusion 32 can be
formed as a raised conical protrusion. As an alternative, other
shapes such as cylindrical shapes may be used. Optionally, a raised
conical protrusion 32 can have a flat upper surface to form a
conical plateau or lower frustum of a cone. As an alternative,
other upper surface shapes and contours may be used.
As shown in FIGS. 1 and 2, the recessed second surface area 30
comprises a central recessed area 34, preferably located in the
center of the bottom face 18, and substantially circular recessed
areas 36 surrounding each of the protrusions 32. In one embodiment,
the recessed second surface area 30, including the central recess
34 and other recesses 36, are recessed at about 1 mm relative to
the surrounding first surface area 28, although the depth of the
recess can vary from about 0.1 mm and less to about 10 mm. As an
example, the recesses 36 surrounding each of the protrusions 32 are
about 5 mm in diameter, although the diameter of the recess can
vary, for example to about 50 mm. The recesses 36 typically provide
an area for the bleb to form. The diameter and arrangement of the
recesses 36 and corresponding protrusions 32 can depend on the
desired delivery characteristics. Other suitable recess
arrangements can be designed depending on the bleb characteristics
desired, the volume of substance to be delivered, the rate of
delivery of the substance, and other factors. As one option, the
diameter of the recess 36 surrounding each of the protrusions 32
can be calculated by one of ordinary skill in the art based on the
volume and rate of the fluid administered.
As shown in FIG. 2, the three protrusions 32 and corresponding
recessed areas 36 are spaced at 120.degree. relative to one another
on the bottom face 18, although arrangements can vary. Some of the
alternative arrangement are shown in further embodiments and
discussed herein. In the embodiment shown, the center of each
protrusion 32 is equally spaced at a distance of about 7.5 mm from
the center of the bottom face 18, although, as discussed above,
other arrangements can be used depending on the desired delivery
characteristics. As an example, the protrusions 32 are about 2 mm
in diameter at the top of the protrusion 32 and may have an
approximately 10.degree. draft from top to base. The draft of the
protrusions 32 can range, for example, from 0.degree. to
60.degree.. The shape and sizes of the protrusions 32 can vary,
although typically, the top of the protrusion will range from 0.5
mm or even smaller to about 10 mm in diameter. The diameter and
shape of the protrusions 32 can be based on, for example,
dermal-access member seating requirements.
In the embodiment shown, one dermal-access member 14 is provided in
each conical protrusion 32, although multiple dermal-access members
14 can be provided in each conical protrusion. Thus, in the
embodiment shown in FIGS. 1 and 2, three dermal-access members 14
are provided.
The upper surface of the raised conical protrusion may be slightly
elevated relative to the first surface area 28, flush with the
first surface area 28, or slightly recessed relative to the first
surface area 28. It is understood that the relative heights of the
respective surfaces may vary depending on desired bleb formation,
skin tensioning characteristics, and dermal-access member seating
requirements. As an exemplary embodiment, the first surface area 28
will be slightly lower than the top of the protrusions, for example
0.25 mm shorter.
Outside of the first surface area 28, the device 10 chamfers to the
outer edge 16 to prevent or reduce edge effect, defined as pressure
applied to the outer edge of the device that may impede performance
of the device 10 or cause the subject discomfort.
In the embodiment shown, each dermal-access member extends about 1
mm from the top of the protrusion 32 with about 0.5 mm to about 2
cm of the dermal-access member remaining within the protrusion 32.
In an exemplary embodiment, the device uses hollow dermal-access
members 14. The dermal-access member tips can be beveled, for
example, at a single bevel angle of approximately 15-35.degree.,
preferably 28.degree..
As shown in FIG. 2, the fluid channel 22 extends between the inlet
24 and the protrusions 32 for supplying a substance to the
dermal-access members 14 or for directing a substance withdrawn
from a subject to a suitable collection container. In one
embodiment, the top face 20 of the body 12 defines the channel 22.
Optionally, the channel 22 is open with respect to the top face 20.
The channel 22 extends from the opening inlet 24 to each of the
dermal-access members 14. In the embodiment shown, the channel 22
includes a central channel 23 from the inlet 24 to the center of
the top face 20 and extends from the center outwardly to each
protrusion 32.
The device 10 can also include a cover portion (not shown in FIGS.
1 and 2) for covering the channel 22. The cover portion may be
glued onto the body 17 with UV cure adhesive or other attachment
mechanism.
In the embodiment shown, the tubing 21 delivers fluid to the
channel 22. The tubing 21 is secured to the inlet end 24 of the
body 12. The tubing 21 may be glued to the coupling member 26.
Optionally, the tubing 21 includes 16 gauge catheter tubing with a
luer fitting (not shown). The other end of the tubing can be
connected to a supply or receiving device. The supply device may be
a syringe (not shown), a unit dose delivery device (not shown), or
a suitable metering pump or infusion device (not shown) for
delivering a substance to device 10 at a controlled rate. This
method can also be used to withdraw a substance from a subject.
In an exemplary embodiment, the channel 22 is smaller than the
tubing 21 feeding the channel 22, but significantly larger than the
exit diameters of the dermal-access members 14 so as not to result
in unnecessary high pressures. The tubing should not be the
limiting factor in the flow of substance through the device.
Optionally, the size and configuration of the dermal-access member
and arrangement of recesses are the primary factors in controlling
substance delivery. The body 12 of the delivery device is
preferably designed to deliver fluids in the range of about 2-5 psi
up to about 200 psi, for example, 50-75 psi. The body 12 can also
be designed to deliver at higher and lower pressures. The body and
all fitting and components of the device should be rigid enough to
withstand pressures on the device without deflection or loss of
liquid sealing.
The device 10 may be taped with tape 38, or otherwise secured, onto
a subject during application. Alternatively, the device can be
manually held in place without any other securing mechanism. The
device 10 can also be designed and/or manufactured with tape or
other suitable securing mechanism, such as an adhesive, as part of
the device 10. Optionally, the device can be installed or
incorporated into an applicator device for mechanically applying
the device to a user.
FIG. 3 illustrates the delivery device of FIGS. 1 and 2 in use,
taped to the subject 40. FIG. 4 shows the bleb pattern resulting
from the application shown in FIG. 3. As shown in FIG. 4,
application of this embodiment of the delivery device results in a
three-bleb pattern.
FIG. 5 shows another embodiment of the device. This embodiment is
similar to the previous embodiment. However, instead of the three
member array shown in FIGS. 1-3, the device shown in FIG. 5
includes a six member array with six protrusions 32 and six
dermal-access members 14.
FIG. 6 shows a further embodiment of the device. Other than the
differences discussed below and illustrated in the Figures, this
embodiment is similar to the other embodiments. This embodiment is
a single member delivery device 10 with one protrusion 32 and one
dermal-access member 14. The device 10 shown in FIG. 6 also differs
from the devices of FIGS. 1-5 in that a flange 44 is provided for
application of adhesive.
In the example shown in FIG. 6, the body 12 is optionally about 3.8
cm or less in diameter, for example, about 1.2 cm. On the center of
the bottom face 18 in the recessed second area 30, the protrusion
32 is formed. In this embodiment, the central recessed area and the
circular recessed area are the same area 30 because only one
centrally located protrusion 32 is provided. One dermal-access
member is installed in the protrusion 32.
A chamfer 42 extends to the edge of the device. The chamfer 42
helps ensure that the proper pressure is applied to the
dermal-access member 14 and prevents any adverse effect of the edge
from the device during delivery.
In the embodiment shown, the flange 44 surrounds the edge 45 for
application of an adhesive ring 46. The flange 44 can, for example,
extend about 1 cm beyond the edge of the device. The flange can be
rigid or flexible and can be designed to extend as far as necessary
beyond the edge of the body 12, depending on the necessary level of
securement and its placement on the subject. The flange 44 should
be slightly recessed relative to the first areas 28 to compensate
for the thickness of the adhesive 46, and to minimize or eliminate
interference with the delivery area. For example, the flange can be
recessed 1 mm although the amount the flange 44 is recessed can
vary. Generally, the adhesive 46 should be located at a distance
from the delivery site, preferably, as far away as is practical, so
as not to interfere with delivery characteristics.
The adhesive 46 is preferably a pressure sensitive adhesive capable
of attaching the device 10 to the surface of the skin of a subject
and is preferably applied directly to the flange 44. The adhesive
46 can be a double-faced adhesive foam tape having one face bonded
to the flange 44. The device 10 is preferably packaged with a
release sheet covering the adhesive 46 that can be removed
immediately before use. As an alternative, any suitable means for
maintaining biological interface of the device with a subject may
be used.
The flange 44 and adhesion arrangement 46 can also be provided in
the other embodiments.
A cover portion 47 is provided to seal the fluid channel 22. The
cover portion 47 has an inside face and an outside face (not
shown). Preferably, the cover portion 47 is circular with a recess
49 on the inside face that accommodates the raised area (not shown
in FIGS. 6 and 7) on the top face of the body 12. As an example,
the cover portion 47 can have a diameter corresponding to the body
12 of the device 10. The recess 49 can be deep enough to
accommodate the corresponding raised area of the body. The recess
49 and raised area of the body act as a locating aid for placement
of the cover portion. The inside of the cover portion 47 can also
define a groove (not shown) which mates with a corresponding rib
(not shown in FIGS. 6 and 7) on the top face of the body 12.
Preferably, the groove is more shallow than the rib to prevent any
possible wicking of adhesive. The rib on the top face allows for
location and alignment of the cover portion 47. The cover portion
47 and raised area can also be designed to account for adhesive
used to adhere the cover portion to the body 12. The cover portion
47 defines a mating half of the fluid channel 22 to allow for
obstruction free insertion of the tubing 21. The cover portion 47
can be of sufficient thickness to help reduce deflection of the
cover portion when pressurized. As an option, the cover portion 47
should not be set on the flange 44, but instead, on the body,
which, as discussed above, is of a rigid design to prevent
deflection.
Shield 48 can be provided for protecting the dermal-access member
14 before use. As shown in FIG. 6, the shield 48 can have a tabbed
lid with three slots to allow it to be press fitted inside the
diameter of the adhesive ring. Alternatively, the shield 48 can
have any suitable design which protects the dermal-access member
prior to use.
FIG. 7 shows the assembled device from FIG. 6.
FIG. 8 shows another embodiment of the invention. This embodiment
is similar to the embodiment shown in FIG. 6. The bottom face 18 of
the body has a six member array of six protrusions 32 and six
dermal-access members 14. The bottom face 18 has a raised first
surface area 28 and a recessed second surface area 30. The
protrusions 32 are provided on the second surface area 30. The
bottom face 18 also has a chamfered surface 42 extending from the
first surface 28 to the edge 43. A flange 44 is provided for
application of adhesive.
FIG. 8 also shows the top face 20 of the body 12. The top face 20
of the body 12 defines a channel 22 for insertion of tubing 21 for
delivery of the fluid. This feature may be present in the other
embodiments, although not clearly shown in previous figures. The
channel 22 may extend from the edge of the main body 12 at inlet
port 24 to the center of the top face 20 of the body 12 and is in
fluid communication with the dermal-access member 14. In the
exemplary embodiment, the tubing extends into the body to a
narrowing stop in the channel. However, the device can be designed
with the tubing extending only to the edge of the device or all the
way through the channel to the dermal-access members. The channel
22 can be, for example, about 1 mm in diameter, although the
channel can be modified depending on the desired delivery
characteristics, including delivery rate and volume. The channel 22
can narrow as necessary to reduce any dead space inside the device
but outside the tubing. For example, the channel can be 0.5 mm in
diameter or less. Dead space results in wasted substance remaining
in the device and not delivered to the subject and/or requires more
pressure than would otherwise be necessary to deliver the substance
to the subject. The top face 20 of the body 12 also has a raised
area 52 on the center of the top face 20. The raised area 52 has a
wall or rib 50 surrounding the fluid channel 22 to enhance sealing
of the channel 22 and to prevent any adhesive from wicking into the
fluid channel during assembly. As an example, the rib 50 can be
about 0.5 mm in height. A cover portion (not shown) can be provided
to enclose the open channel.
FIG. 9 is an enlarged perspective view of the bottom face of
another embodiment. The bottom face 18 of the body 12 shown in the
embodiment of FIG. 9 is similar to the device shown in FIG. 6. The
embodiment of FIG. 9 is a single member array with a single
protrusion 32. Instead of being a conical protrusion, the
protrusion 32 has arms extending at 120.degree. from one another.
The device of FIG. 9 has a three portion first surface area 28 and
an edge 16 that chamfers to the flange 44.
As shown by the alternate protrusion shown in FIG. 9, the
protrusions of any of the embodiments can be any suitable shape or
arrangement to achieve optimal results. For example, the
protrusions can have cylindrical, pyramidal, or other geometrical
configurations. As a further alternative, the protrusions can be
arranged as a type of sleeve supporting the dermal-access member
which retracts upon application. The protrusions can be arranged on
a flexible hinge region, such as a flexible membrane or temperature
sensitive polymer, which also retracts in a longitudinal direction
upon application. In addition, the upper surface of the protrusion
can be flat, concave or convex. Alternatively, the dermal-access
member can be supported directly on the second surface area without
any protrusion or with a protrusion that provides minimal
support.
FIG. 10 is a perspective view of the top 20 and bottom 18 faces of
another embodiment of the present invention. The device shown in
FIG. 10 is a three member array with three protrusions. Instead of
having a longitudinal channel defined on the top face of the body,
which extends from the edge of the device to a dermal-access
member, the embodiment of FIG. 10 has individual channels 25 in
fluid communication with the dermal-access members (not shown in
FIG. 10). In the embodiment shown, the individual channels 25
extend perpendicularly directly from the top face 20 to the
protrusions 32 and the dermal-access members. Any suitable
mechanism, such as a syringe or pump, can be used to deliver or
extract fluid from the individual channels 25. Individual channels
22 can be useful in delivering different fluids to a subject or
delivering fluids at different pressures. For example, as shown in
FIG. 10, three separate delivery means could deliver fluid to the
device.
FIG. 11 is a perspective view of the top 20 and bottom faces 18 of
another embodiment of the present invention. The device shown in
FIG. 11 is a three point array with three protrusions 32. Instead
of having a longitudinal channel defined on the top face of the
body which extends from the edge of the device to a dermal-access
member, the embodiment of FIG. 11 has a reservoir 23 defined on the
top face 20. Fluid is introduced from the relatively shorter
longitudinal channel into the reservoir 32. The fluid is
communicated from the reservoir 32 to the dermal-access member (not
shown in FIG. 11).
FIGS. 12-15 show still further embodiments of the device.
Generally, the embodiments shown in FIGS. 12-15 are smaller than
those shown in FIGS. 1-3 and 5-11.
The device 10 shown in FIGS. 12 and 13 is a three member array with
a bottom face 18 having three protrusions 32 and a flange 44. As
shown in FIG. 12, the dermal-access members have not yet been
installed. The top face 20 has a raised portion 54 at least in part
defining flow paths to the protrusions and configured to receive a
cap assembly 53. The cap assembly 53 and tubing 21 for delivering
the fluid to the patient during use is shown in FIG. 13.
As an example, the device 10 shown in FIGS. 12 and 13 has a
thickness of about 5 mm and a diameter of about 18 mm with the
flange 44. The body chamfers at 45.degree. to the flange 44. The
protrusions 32 extend slightly above the raised first surface area
28, for example about 0.2-0.3 mm above the first surface area 28.
The top face of each of the protrusions 32 is about 2 mm in
diameter. The protrusions 32 are spaced equally around the center
of the top face 20, and the distance from the center of a
protrusion 32 to the center of the device 10 is 2.5 mm.
The device 10 shown in FIG. 14 is a single dermal-access member
device with a bottom face 18 having a single dermal-access member
installed in the protrusion 32. The top face 20 has a raised
portion 54 at least in part defining a flow path to the protrusion
and configured to receive a cap assembly (not shown).
By way of example, the device 10 shown in FIG. 14 is about 5 mm
thick and has a diameter of about 18 mm with the flange 44. The
protrusion 32 extends slightly above the raised first surface area
28, for example about 0.2-0.3 mm above the first surface area 28.
The top face of the protrusion 32 is about 2 mm in diameter.
The device 10 shown in FIG. 15 is a three dermal-access member
linear array with a bottom face 18 having three protrusions 32. The
top face 20 has a raised portion 54 at least in part defining flow
paths to the protrusions and configured to receive cap assembly
(not shown). The dermal-access members are not yet installed in
FIG. 15. Both the device 10 and body 12 are elliptical.
By way of example, the elliptical embodiment of the device 10 shown
in FIG. 15 is about 5 mm thick and has length of about 19.5 mm and
a width of about 23 mm. The body 12 has a length of about 15 mm and
a width of about 9 mm. The protrusions 32 extend slightly above the
raised first surface area 28, for example about 0.2-0.3 mm above
the first surface area 28. The top faces of the protrusions 32 are
about 2 mm in diameter, and the center of a protrusion is spaced
about 3 mm from an adjacent protrusion.
Another embodiment of the dermal-access member array is shown in
FIG. 16. It includes a linear dermal-access member array with a
manifold 33 for holding the protrusions 32 and dermal-access
members 14 having a rectangular face and a generally parallelpiped
shape. Typically, the embodiment shown in FIG. 16 is integrated
into device 10. Other than the protrusions, the embodiment of FIG.
16 has a planar face. The face can have a length of about 4.8 mm,
and a width of about 11 mm. The protrusions have a linear
arrangement and are spaced about 3 mm apart from one another. The
diameter of the conical protrusions are relatively small, for
example, about 0.95 mm or smaller.
The arrangement and relative heights of the dermal-access members,
recesses, and protrusions can be modified to accomplish or
emphasize any number of intended beneficial characteristics of the
invention. Specifically, the length, width and spacing of the
dermal-access members can vary depending on the pharmaceutical
agent being administered or required to penetrate the skin to the
optimum depth for the specific pharmaceutical or bioactive agent
being administered. The device of the present invention maximizes
the effective penetration of dermal-access members to a targeted
depth. The device can control the size of the bleb. In a device
with multiple dermal-access members, the device can be engineered
to control the instillation patterning of individual blebs and
their relationship to each other. Non-communication between
individual dermal-access members can be meaningful for deposition
of large volumes in a broad biological space or the deposition of
multiple fluids, or in designing the pressure parameter of a
dermal-access member. The device can be designed to provide
sufficient fluid flow path to accommodate the desired velocity and
rate of fluid to be instilled and to minimize the amount of void
volume. The device can further be designed as a function of the
desired bleb pattern and for application of a particular fluid at a
particular site to minimize the area of application.
Generally, the patterning of the dermal-access members can be
designed to achieve desired characteristics. Typically, a minimal
number of dermal-access members can be used to reduce the pain or
the perception of pain by a subject, manufacturing complexity or
cost, the number of potential failure points, the complexity of the
device fluid dynamics, and the dose lost to void volumes in the
device or system. The number of dermal-access members can be
increased to decrease the possibility of blocked fluid paths, to
increase the distribution area of instilled fluid to accommodate a
greater volume or delivery rate, and to potentially increase
uptake.
Alternate arrangements for delivering fluid to the dermal-access
members include but are not limited to multiple reservoirs; a
manifold arrangement in which fluid is communicated from a
reservoir, through individual channels to the dermal-access
members; and independent channels. In addition, the channels can be
provided with individual or combination valving or other means for
fluid flow rate control.
As discussed above, the number and arrangement of dermal-access
members and protrusions in each of the embodiments can depend on
the desired range of fluid delivery volume. Furthermore, the
recessed second surface area surrounding each protrusion can be
arranged based on the desired range of fluid delivery volume. For
example, a three member array that delivers 100 .mu.l of fluid may
have recesses surrounding each dermal-access member of
approximately 5 mm in diameter. Conversely, a single member array
that delivers 100 .mu.l of fluid may have a recess surrounding the
single dermal-access member with an approximately 10 mm diameter.
As discussed above, the size and arrangement of the recesses depend
on the desired flow characteristics, including the volume and rate
of delivery of the substance.
A method for delivering or withdrawing a substance through the skin
is also provided. The device is positioned in a target site on the
surface of a subject's skin. The body is pressed downwardly against
skin with a pressure sufficient to cause dermal-access members to
penetrate the layers of skin. The depth of penetration is dependent
upon the length of dermal-access members, the spacing of the
dermal-access members, and the dimensions of the body, including
the height of the protrusion, pressure exerted on the device, and
the tensioning of the skin resulting from the body.
The skin of a subject has elastic properties that resist
penetration by the dermal-access members. The skin can be stretched
by the raised first surface area until the skin is taut before the
dermal-access members penetrate the skin. A penetrating pressure
can be applied to the device until the first surface area contacts
the skin. This promotes uniform penetration of the skin by each of
the dermal-access members. Consequently, when the device is secured
to skin with either a manual application or adhesive, a pressure is
constantly applied to dermal-access members 14.
A substance is supplied to the device and fed to dermal-access
members for delivery to the subject. In alternative embodiments, a
substance is withdrawn from the subject in a similar manner.
For a bolus type injection, the spacing of the delivery points is
not as important because the pressure is higher and delivery occurs
at each dermal-access member approximately simultaneously.
Dermal-access member spacing in the bolus type injection may
determine whether a single bleb or multiple blebs form.
For lower rate deliveries, it is beneficial to ensure that the
delivery points are spaced close enough together to create a single
bleb. As delivery at a particular dermal-access member in a
multi-dermal-access member device begins, the pressure at that
particular dermal-access member decreases. At relatively low
delivery pressures, if the dermal-access members are spaced too far
apart, the first dermal-access member to form a bleb will be the
preferential path because the substance to be delivered will
inherently follow the path of least resistance. Thus, by having all
the points feed the same bleb, no preferential flow through a
particular dermal-access member or delivery point should occur
because pressure will be equalized across the dermal-access
members.
The device of the invention can remain interfaced with the skin for
sufficient time to withdraw from or deliver to the subject the
desired substances. The length of time the device is required to be
attached or in communication with the skin of the subject is
usually dependent on the substance being delivered or withdrawn,
the volume of the substance, the target area on the skin, the depth
of penetration, and the number and spacing of dermal-access
members. The amount of time the device is secured to the skin may
reduce the amount of leakage from the skin after delivery of the
fluid.
Many of the considerations in designing the device of the present
invention involve proper placement of the dermal-access members,
including placement of the dermal-access members at the proper
depth. Specifically, pharmacokinetics (PK) for certain classes of
medicaments can be improved by administering the medicament at a
specified place below the stratum corneum.
Generally, deposition in intradermal tissue results in faster drug
onset kinetics for system uptake and bioavailability, and increased
bioavailability for some drugs. However, intradermal delivery is
limited in that intradermal tissue space is highly compact and has
limitations on the total amount of volume which can be
administered, the rate at which such fluid can be administered, and
the pressure required to administer such volume. Generally, the
subcutaneous layer is not well perfused by capillaries. As such,
absorption is both slower, and in some cases, decreased
bioavailability.
Thus, the PK outcome of dermal-access delivery is specific to the
deposition depth and patterning of the administered fluid and such
deposition can be mechanically controlled via design of the device
of the present invention. It has been shown that delivery of
medicaments to two different depths increases the PK benefits, for
example, delivery to both shallow subcutaneous areas and
intradermal areas.
The present invention can include a device to deliver the
medicament to two different depths, and specifically, to two
different physiological tissue compartments, such as shallow
subcutaneous and intradermal. This can be accomplished, for
example, by dermal-access members of different lengths. Other
geometric or mechanical mechanisms can also be designed to deliver
fluids to different depths. The device can also be provided with
flow restrictors to deliver differing amounts of fluid to different
areas.
For each of the embodiments discussed herein, the device is
optionally radiation stable to allow for sterilization, if
radiation is to be used. Optionally, the body should be transparent
or translucent to allow for light to penetrate and cure the UV
adhesive holding the dermal-access member secure. As another
option, the body can be opaque and epoxy can be used to secure the
dermal-access member. It is noted that having a transparent body
enables a user or other person administrating the device to
properly prime the device by ensuring that no excess air is in the
device. Furthermore, the body and cover portion material should be
stiff enough so as not to deflect during normal use conditions and
should be able to withstand internal fluid pressure in the range of
about 2-5 psi to about 200 psi without failure or leaks. However,
the flange and adhesive can be as flexible as necessary for
comfortable and secure attachment to the subject. The body and
cover portion material can selected to be non-affected by the drug
and having no effect on the drug candidates to be used. The body
and the cover portion material should also be hypoallergenic.
The device of the invention can optionally be used as a disposable,
single-use device. The device can be sterilized and can be stored
in a suitable sterile package.
Adequate dermal-access member seating is an important aspect of the
present invention. Successful dermal-access member seating is
defined as positioning the dermal-access members in the skin such
that fluid delivered through the dermal-access member or
dermal-access members does not leak out of the skin.
Generally, there are four factors which contribute to a desirable
dermal-access member seating: dermal-access member length,
dermal-access member protrusion geometry, dermal-access member
overtravel, and the dermal-access member seating velocity.
Overtravel is defined as the extent that the upper face of the
protrusion extends beyond the adhesive or other securing mechanism
of the device i.e., the bottommost face of the device. The
embodiment shown in FIG. 12 has an overtravel of about 1 mm,
although more or less overtravel amounts can be adequate to ensure
proper dermal-access member seating, for example, about 0.5 mm. Of
course, it is also important to avoid any obstructions on the body
face.
Exemplary embodiments of the geometry of the device in general and
of dermal-access member manifolds have been discussed above.
Experiments have shown that smaller protrusion diameters increase
the effectiveness of dermal-access member seating. It was believed
that the higher local pressure exerted by the smaller surface of
the protrusion for a given force contributes to the beneficial
dermal-access member seating. It is further believed that the
smaller surface area of the face of the protrusion has a smaller
local effect on the development of the bleb.
In one such experiment, a device was applied to a swine test
subject to determine the effectiveness of smaller diameter
protrusions as compared to larger diameter protrusions. The
experiment was conducted at a constant delivery pressure of 15 psi,
with a 50 .mu.L air bolus, and with needles as the dermal-access
members. The protrusions are conical protrusions with a flat top
surface. The dermal-access members extend 1 mm above the top
surface of the protrusion. Although the surface is flat in this
experiment, as noted above, the top surface of the protrusion can
be concave or convex. If the top surface is concave, the length of
the dermal-access member is measured from the outer rim of the top
surface to the top of the dermal-access member. If the top surface
is convex, the length of the dermal-access member is measured from
the uppermost tangent of the surface to the top of the
dermal-access member.
In the aforementioned experiment, the smaller diameter protrusions
are about 1 mm (0.0375") in diameter and the larger diameter
protrusions are about 2 mm (0.075") in diameter. The experiment
also accounted for varying amounts of overtravel. The results are
shown in FIG. 17. Column "over" describes the amount of overtravel
in thousandths of an inch. Column "leaker" states whether the trial
leaked or not. Column "bleb type" describes the number and
particulars, if any. Column "average rate" describes the average
steady-state flow rate calculated in .mu.L/min. The average rate of
a trial that leaked is 0. Column "if no leaks" shows the average
rate of the properly seated trials.
As can be seen from FIG. 17, the smaller diameter protrusions
provided better needle seating. In addition, overtravel was shown
to be a factor in needle seating. The experiment suggested that
overtravel greatly prevents leaking.
Interestingly, overtravel did not seem to negatively affect
infusion rates. This was somewhat surprising, given the previous
experience with overdriven or overtraveled needles. It has been the
conventional experience when using 1 mm needles mounted in catheter
tubing that pushing the catheter into the skin significantly
affects the pressure required to infuse at a given rate in a
constant pressure system. However, the amount of overtravel
necessary to produce this effect is likely larger than the maximum
overtravel of 0.040" seen in this experiment. This suggests an
optimal overtravel amount which can be discerned from further
experiments.
It has further been shown that an increased velocity in the
application of the dermal-access members can increase the
effectiveness of the seating.
An applicator for mechanically applying the device to a patient can
control the velocity of the dermal-access members. For example, an
applicator such as a Minimed SOF-SERTER.TM. insertion device or a
BD INJECT-EASE.TM. device can be modified to apply the device to a
user at a desired velocity. The device is driven toward the skin by
springs contained in the applicator and results in the
dermal-access members seating into the skin of a subject. Among
other factors, the strength of the springs determines the velocity
of the dermal-access members.
Experiments have shown that there is a continuum of velocity ranges
within which dermal-access member seating improves with velocity,
for a given skin type, manifold mass, and needle sharpness.
Initial seating experiments in Yorkshire pigs utilized a single
spring rate of about 5 lbf/in. This allowed a 1.7 gram manifold to
be propelled at about 6.3 m/s. At this velocity, most 1 mm and 3 mm
dermal-access members seated without leaking. However, a large
number of manifolds did not have enough energy to seat the
dermal-access members to the required depth. Heavier manifold
tests, from a drop-center design, had velocities of about 3 m/s. At
this velocity, most of the 1 mm dermal-access members leaked.
Similarly, most of the 3 mm dermal-access members produced very
shallow blebs. One manifold arrangement uses two springs with
spring constants of 3.2 lb/in, and is less massive than other
manifolds. This manifold arrangement enables a manifold velocity of
about 12 m/s or greater. With this arrangement, nearly 100% of the
dermal-access members seated properly. Accordingly, it has been
shown that, for this arrangement, a velocity of about 6 m/s to 18
m/s is ideal, optionally about 6 m/s to about 25 m/s. It is noted,
however, that these resultant, calculated velocities were
calculated based on energy conservation equations based on known
initial forces, and does not account for any friction within the
applicator or friction of the dermal-access members passing through
the skin. The actual velocities in this example could be much less,
for example, 50% less.
One experiment determining dermal-access member velocity utilizes a
mechanical applicator in which a device with a three dermal-access
member manifold is loaded. In this experiment, 34 gauge
dermal-access members are used. A coil spring is placed on a post
of the manifold to tension the manifold in the applicator. A luer
and line arrangement can supply fluid to the manifold at a constant
pressure. The applicator is placed on a swine, the applicator is
activated to release the spring to drive the manifold with the
dermal-access members into the skin, and fluid is delivered to the
subject. In this experiment, the manifold is driven about 5 mm. The
following parameters were considered:
Springs Force: None; Low: 1 lb. initial spring force, 0.5 lb. final
force; or High 2 lb. initial spring force, 1 lb. final force
Device: Center or Side
Adhesive: Full or Missing (safety)
Septum: With or Without
Member Length: 1 mm or 3 mm
The results are shown in FIGS. 18A-D. As can be seen, needle
seating increases with velocity.
The following is a description of a further experiment
demonstrating the importance of dermal-access member velocity. The
tests were conducted to determine the more effective dermal-access
member seating arrangement between a side push microinfuser and a
drop-center infuser. The drop-center manifold ("heavy") weighs
about 7.8 grams, and the side push manifold weights about 0.4-0.6
g. Therefore, for a given spring or spring set used to drive the
manifold, the drop-center design will be at least 10 times slower
in its initial velocity than the side push design. For this
experiment, manifolds weighing about 1.7 grams were used as "light"
manifolds. The results are shown in FIG. 19. For the 3 mm
dermal-access members, the light manifolds had an average flow rate
of about 3 times than that of the heavy manifolds. This indicates
that for the 3 mm needles, the heavy manifold seated the needles to
a considerably shallower depth than the light manifold. This is
because shallower infusions are known to have a higher back
pressure than deeper infusions. The differences shown in the 1 mm
dermal-access members were even greater, and none of the heavier 1
mm manifolds were successfully seated.
The lack of obstructions on the face of the device has also been
shown to increase effective dermal-access member seating. For
example, the exemplary embodiment shown in FIG. 16 has a single
surface, i.e., without the raised or recessed first or second
surface areas discussed in previous embodiments. The effectiveness
of needle seating for an obstructionless device face was shown in a
further experiment. The device of FIG. 16 was incorporated into a
mechanical applicator for applying the device to a subject at a
constant pressure, constant volume, constant dermal-access member
length and constant overtravel amount. The leakage rates for these
trials were compared to those of trials using a device identical to
that shown in FIG. 16, except that the device had walls extending
around the periphery of the bottom face of the device, flush with
the walls of the parallepiped shaped and at a height equal to that
of the tops of the protrusions. The device with the walls leaked
more often than the device without walls. It was determined that
the presence of a wall on the device only hurts infusion
reliability. It is believed that the wall limits the amount of
overtravel of the device, and further, prevents the skin in the
immediate proximity of the protrusions from wrapping around the
protrusions. This agrees with the results of the experiment
depicted in FIG. 17 and discussed above.
While various embodiments have been chosen to illustrate the
invention, it will be appreciated by those skilled in the art that
various additions and modifications can be made to the invention
without departing from the scope of the invention as defined in the
appended claims. For example, the body of the device may be made as
an integral one-piece unit. In alternative embodiments, the body
can be made from separately molded sections or pieces and assembled
together. The molded sections can be assembled using an adhesive,
by welding, or by the use of mechanical fasteners. Additionally,
any number of dermal-access members may be provided on the
device.
* * * * *